Pemphigus foliaceus, the most common autoimmune skin condition in dogs and cats, is characterized by pustules, erosions, and crusts. In this article, we focus on the diagnosis and treatment of pemphigus foliaceus in dogs and cats.

PATHOGENESIS

Pemphigus foliaceus affects the epidermis, the outermost superficial skin layer. To help the epidermis act as a barrier to the outside world, the epidermis is composed primarily of tightly adherent keratinocytes. Two types of adhesion structures hold keratinocytes together. Desmosomes are responsible for cell-to-cell adhesion. Hemidesmosomes are responsible for cell-to-matrix adhesion. In the skin, hemidesmosomes bind the deep or basilar epidermal keratinocytes to the basement membrane.

The pemphigus variants occur when autoantibodies target the desmosomes between keratinocytes. Desmosome disruption results in separation of the keratinocytes, which is referred to as acantholysis. Keratinocytes that have lost their cell-to-cell adhesion are called acantholytic keratinocytes, not acanthocytes (i.e. crenated red blood cells).

In pemphigus foliaceus in people, the most common target of autoantibodies is the desmoglein 1 (DSG1) glycoprotein in the desmosome.1,2 The autoantibody response primarily involves IgG (IgG4 subclass).3 Initial studies in dogs with pemphigus foliaceus only rarely detected an IgG autoantibody response,4,5 but more recent work using different substrates in indirect immunofluorescence testing confirms that IgG autoantibodies are important in canine pemphigus foliaceus.6 However, DSG1 is not commonly targeted in pemphigus foliaceus in dogs7 ; it is not yet known which part of the desmosome is targeted in most canine pemphigus foliaceus cases. Early immunoblotting studies revealed that the target was a 148 kDa or 160 kDa protein.8,9 Immunoelectron microscopy shows that the site of autoantibody binding is in the extracellular region of the desmosome.10

The word pemphigus is used for the entire group of autoimmune blistering diseases in which intraepidermal separation occurs via acantholysis. Pemphigus foliaceus is a specific type of superficial pemphigus and is clinically distinct from deep pemphigus diseases. Another example of superficial pemphigus disease is pemphigus erythematosus. Examples of deep pemphigus diseases include paraneoplastic pemphigus, pemphigus vulgaris, and bullous pemphigoid.

The signs of an attack on keratinocyte adhesion structures are clinically evident. When the tight bonds between superficial keratinocytes are affected, it manifests as vesicles and pustules. When the tight bonds between basilar keratinocytes and the skin's basement membrane are affected, it manifests as bullae (large blisters) and ulcers.

More recently, pemphigus foliaceus has been proposed as the general term for all superficial pemphigus diseases, since there is an overlap in clinical, histologic, and immunologic characteristics among all the superficial pemphigus conditions.11 Deep pemphigus conditions, though, still remain clinically and immunologically distinct from the superficial pemphigus conditions. Thus, the term pemphigus should not be used as a diagnosis by itself for any patient because it refers to a heterogeneous group of both superficial and deep pemphigus conditions.

SIGNALMENT AND CAUSES

Genetic factors can influence the development of pemphigus foliaceus. In dogs, it is more frequently diagnosed in two breeds with closely related genotypes,12 Akitas and chows.4 Pemphigus foliaceus has also been reported in littermates.13 No breed disposition has been noted in feline pemphigus foliaceus.

Sex and age appear to be unrelated to the development of pemphigus foliaceus in dogs and cats. The age of onset is variable and ranges from 1 to 16 years in dogs4,5,14 and less than 1 year of age4 to up to 17 years of age15 in cats.

Ultraviolet light

Ultraviolet exposure from the sun is a potential environmental trigger for pemphigus foliaceus. The skin lesions in dogs with pemphigus foliaceus can worsen in the summer and improve in the winter.16,17 Exposing dogs with facial pemphigus foliaceus to ultraviolet B (UVB) results in increased epidermal acantholysis.18 We think there is a lower prevalence of canine pemphigus foliaceus in cooler U.S. regions compared with warmer U.S. regions with more sun exposure.